Premature, very-low-birth-weight (VLBW; d1500 g) and low-birth-weight (LBW; 1500-2499 g) infants are at increased risk for long-term encephalopathy. 25-50% of the 63,000 VLBW infants born annually in the U.S. have major long-term cognitive or neurobehavioral deficits. Postnatal cerebral ischemia appears to play an important role in long-term cognitive sequelae. Unfortunately, the ability of the cerebral vasculature of LBW and VLBW neonates to maintain adequate cerebral blood flow is poorly understood. Although important, provocative clinical studies have been performed with classical Kety-Schmidt methodology, Doppler ultrasound, positron emission tomography, perfusion computed tomography, magnetic resonance imaging and near-infrared spectroscopy, there is currently no technique for easily, repeatedly and noninvasively monitoring or measuring cerebral circulatory adequacy in LBW or VLBW infants. Our start-up company, Noninvasix, recently demonstrated in VLBW and LBW infants that optoacoustic technology permits easy, accurate, direct noninvasive measurement of cerebral venous blood oxygen saturation in the superior sagittal sinus (SSSSO2) through the open anterior fontanelle. SSSSO2 measures the ability of cerebral blood flow to meet cerebral oxygen demand; in adults with traumatic brain injury cerebral venous saturations less than 50%, suggesting that cerebral blood flow does not meet cerebral oxygen demand, have ominous prognostic implications. Having established the proof-of-concept for optoacoustic SSS monitoring of neonates, we now propose in this Phase I application to refine that technique as a major step toward commercialization of a device for intermittent measurements and continuous monitoring of neonatal cerebral perfusion. In this Phase I proposal, based on our laboratory prototype, Noninvasix will collaborate with The University of Texas Medical Branch, which co-owns Noninvasix with two faculty who are inventors and investigators in this proposal, and Cooper Consulting Services (CCS), an engineering design firm, to iteratively design and build a clinical prototype neonatal interface and a user interface and test it in post- delivery neonates. We will produce and test the clinical prototype (Fig. 1 in Innovation section) by progressing through the following specific aims: Specific Aim 1. To develop a clinical prototype patient interface for our noninvasive optoacoustic monitor that will accurately determine SSSSO2 in neonates. Specific Aim 2. To develop a clinical user interface for our noninvasive optoacoustic monitor that will facilitate rapid assessment of SSSSO2 in neonates intermittently or continuously in the Neonatal Intensive Care Unit. Specific Aim 3. Preliminarily establish in vivo in neonates the range of SSSSO2 to be expected in infants of varying body weight (10-12 LBW neonates and 10-12 VLBW neonates).